A supramolecular basis for CD45 tyrosine phosphatase regulation in sustained T cell activation
A supramolecular basis for CD45 tyrosine phosphatase regulation in sustained T cell activation
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DOI：
10.1073/pnas.97.18.10138
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发表时间：
2000-08-29
影响因子：
11.1
通讯作者：
Thomas, ML
中科院分区：
文献类型：
--
作者：
Johnson, KG;Bromley, SK;Thomas, ML
跨膜蛋白酪氨酸磷酸酶，如CD 45，可以作为细胞信号传导的正和负调节剂。CD 45通过C-末端负调节磷酸酪氨酸位点的去磷酸化而组成性地引发p56 lck，从而正向调节T细胞受体（TCR）信号传导。然而，CD 45也可以对细胞过程产生负面影响，包括由整合素介导的粘附引发的事件。为了更好地理解酪氨酸磷酸酶的这些相反作用，通过使用激光扫描共聚焦显微镜在活T淋巴细胞的功能性TCR信号传导期间对CD 45的亚细胞区室化进行成像。在抗原接合时，CD 45首先从T细胞和抗原呈递表面之间的界面的中心区域排除，在该区域中CD 45将抑制整联蛋白活化。随后，CD 45被募集回到接触中心，到达与持续TCR接合位点相邻的区域。因此，CD 45很好地定位在接合的TCR附近的超分子组装体内，其中CD 45将能够在TCR接合的持续时间内维持src-激酶活性。
Transmembrane protein tyrosine phosphatases, such as CD45, can act as both positive and negative regulators of cellular signaling. CD45 positively modulates T cell receptor (TCR) signaling by constitutively priming p56lck through the dephosphorylation of the C-terminal negative regulatory phosphotyrosine site. However, CD45 can also exert negative effects on cellular processes, including events triggered by integrin-mediated adhesion. To better understand these opposing actions of tyrosine phosphatases, the subcellular compartmentalization of CD45 was imaged by using laser scanning confocal microscopy during functional TCR signaling of live T lymphocytes. On antigen engagement, CD45 was first excluded from the central region of the interface between the T cell and the antigen-presenting surface where CD45 would inhibit integrin activation. Subsequently, CD45 was recruited back to the center of the contact to an area adjacent to the site of sustained TCR engagement. Thus, CD45 is well positioned within a supramolecular assembly in the vicinity of the engaged TCR, where CD45 would be able to maintain src-kinase activity for the duration of TCR engagement.